Members of the Flaviviridae family that infect humans frequently cause severe morbidity and mortality, and epidemics of flaviviruses continue to be a major public health concern worldwide. Over half of the at least 70 distinct virus species of the genus Flavivirus are associated with human disease, and in all, more than two billion people are at risk of being infected with members of the genus. The medically important flaviviruses include yellow fever (YF) virus (predominantly in Africa, Latin and South America); Japanese encephalitis (JE) virus (predominantly in Asia and Australia); West Nile (WN) virus (predominantly in Africa, Central Europe, and most recently in North America); tick-borne encephalitis (TBE) complex viruses (predominantly in temperate regions worldwide); and the four serotypes of dengue viruses (DEN-1, -2, -3, and -4) (predominantly in tropical and subtropical regions of the world) (Lindenbach & Rice, Flaviviridae: the viruses and their replication. In Fields Virology, 4th ed., Knipe and Howley. Eds., Philadelphia, Lippincott Williams & Wilkins, pp. 991-1041, 2001; Burke & Monath, Flaviviruses. In Fields Virology, 4th ed., Knipe and Howley. Eds., Philadelphia, Lippincott Williams & Wilkins, pp. 1043-1125, 2001; Kuno et al., J. Virol. 1998, 72, 73-83, 1998; Solomon & Mallewa, J. Infect. 42:104-15, 2001).
West Nile Virus (WNV) outbreaks in particular have increased markedly in frequency and severity. Since first appearing in New York City in 1999, the virus has spread to the entire continental United States with outbreaks occurring each subsequent summer.
Another member of the Flaviviridae family causes hepatitis, which affects nearly 750,000 Americans each year, and out of those, more than 150,000 are infected with the hepatitis C virus (HCV). HCV is most closely related pestiviruses, which include hog cholera virus and bovine viral diarrhea virus (BVDV).